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Journal For Immunotherapy of Cancer Apr 2023Immunotherapy has revolutionized the treatment of cancer. In particular, immune checkpoint blockade, bispecific antibodies, and adoptive T-cell transfer have yielded... (Review)
Review
Immunotherapy has revolutionized the treatment of cancer. In particular, immune checkpoint blockade, bispecific antibodies, and adoptive T-cell transfer have yielded unprecedented clinical results in hematological malignancies and solid cancers. While T cell-based immunotherapies have multiple mechanisms of action, their ultimate goal is achieving apoptosis of cancer cells. Unsurprisingly, apoptosis evasion is a key feature of cancer biology. Therefore, enhancing cancer cells' sensitivity to apoptosis represents a key strategy to improve clinical outcomes in cancer immunotherapy. Indeed, cancer cells are characterized by several intrinsic mechanisms to resist apoptosis, in addition to features to promote apoptosis in T cells and evade therapy. However, apoptosis is double-faced: when it occurs in T cells, it represents a critical mechanism of failure for immunotherapies. This review will summarize the recent efforts to enhance T cell-based immunotherapies by increasing apoptosis susceptibility in cancer cells and discuss the role of apoptosis in modulating the survival of cytotoxic T lymphocytes in the tumor microenvironment and potential strategies to overcome this issue.
Topics: Humans; Immunotherapy; Neoplasms; Immunotherapy, Adoptive; T-Lymphocytes, Cytotoxic; Apoptosis; Tumor Microenvironment
PubMed: 37055217
DOI: 10.1136/jitc-2022-005967 -
Cells Jun 2023The pervasive application of chimeric antigen receptor (CAR)-based cellular therapies in the treatment of oncological diseases has long been recognized. However, CAR T... (Review)
Review
The pervasive application of chimeric antigen receptor (CAR)-based cellular therapies in the treatment of oncological diseases has long been recognized. However, CAR T cells can target and eliminate autoreactive cells in autoimmune and immune-mediated diseases. By doing so, they can contribute to an effective and relatively long-lasting remission. In turn, CAR Treg interventions may have a highly effective and durable immunomodulatory effect via a direct or bystander effect, which may have a positive impact on the course and prognosis of autoimmune diseases. CAR-based cellular techniques have a complex theoretical foundation and are difficult to implement in practice, but they have a remarkable capacity to suppress the destructive functions of the immune system. This article provides an overview of the numerous CAR-based therapeutic options developed for the treatment of immune-mediated and autoimmune diseases. We believe that well-designed, rigorously tested cellular therapies could provide a promising new personalized treatment strategy for a significant number of patients with immune-mediated disorders.
Topics: Humans; Receptors, Antigen, T-Cell; Immunotherapy, Adoptive; Autoimmune Diseases; Immunomodulation
PubMed: 37296654
DOI: 10.3390/cells12111534 -
Cancer Treatment Reviews Nov 2021Multiple systemic treatments are currently available for advanced cancers of the digestive tract, but none of them is curative. Adoptive T-cell immunotherapy refers to... (Review)
Review
Multiple systemic treatments are currently available for advanced cancers of the digestive tract, but none of them is curative. Adoptive T-cell immunotherapy refers to the extraction, modification and re-infusion of autologous or allogenic T lymphocytes for therapeutic purposes. A number of clinical trials have investigated either non-engineered T cells (i.e., lymphokine-activated killer cells, cytokine induced killer cells, or tumor-infiltrating lymphocytes) or engineered T cells (T cell receptor-redirected T cells or chimeric antigen receptor T cells) in patients with digestive tract malignancies over the past two decades, with variable degrees of success. While the majority of completed trials have been primarily aimed at assessing the safety of T-cell transfer strategies, a new generation of studies is being designed to formally evaluate the antitumor potential of adoptive T-cell immunotherapy in both the metastatic and adjuvant settings. In this review, we provide an overview of completed and ongoing clinical trials of passive T-cell immunotherapy in patients with cancers of the digestive tract, focusing on present obstacles and future strategies for achieving potential success.
Topics: Digestive System Neoplasms; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen
PubMed: 34525422
DOI: 10.1016/j.ctrv.2021.102288 -
BMJ (Clinical Research Ed.) May 2024In addition to conventional chemoradiation and targeted cancer therapy, the use of immune based therapies, specifically immune checkpoint inhibitors (ICIs) and chimeric... (Review)
Review
In addition to conventional chemoradiation and targeted cancer therapy, the use of immune based therapies, specifically immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T cell therapy (CAR-T), has increased exponentially across a wide spectrum of cancers. This has been paralleled by recognition of off-target immune related adverse events that can affect almost any organ system including the cardiovascular system. The use of ICIs has been associated with myocarditis, a less common but highly fatal adverse effect, pericarditis and pericardial effusions, vasculitis, thromboembolism, and potentially accelerated atherosclerosis. CAR-T resulting in a systemic cytokine release syndrome has been associated with myriad cardiovascular consequences including arrhythmias, myocardial infarction, and heart failure. This review summarizes the current state of knowledge regarding adverse cardiovascular effects associated with ICIs and CAR-T.
Topics: Humans; Neoplasms; Immune Checkpoint Inhibitors; Immunotherapy, Adoptive; Cardiovascular Diseases; Cardiotoxicity; Myocarditis; Cytokine Release Syndrome; Pericarditis
PubMed: 38749554
DOI: 10.1136/bmj-2023-075859 -
Current Stem Cell Research & Therapy 2022Natural Killer (NK) cells were initially described in the early 1970s as major histocompatibility complex unrestricted killers due to their ability to spontaneously kill... (Review)
Review
Natural Killer (NK) cells were initially described in the early 1970s as major histocompatibility complex unrestricted killers due to their ability to spontaneously kill certain tumor cells. In the past decade, the field of NK cell-based treatment has been accelerating exponentially, holding a dominant position in cancer immunotherapy innovation. Generally, research on NK cell-mediated antitumor therapies can be categorized into three areas: choosing the optimal source of allogeneic NK cells to yield massively amplified "off-the-shelf" products, improving NK cell cytotoxicity and longevity, and engineering NK cells with the ability of tumor-specific recognition. In this review, we focused on NK cell manufacturing techniques, some auxiliary methods to enhance the therapeutic efficacy of NK cells, chimeric antigen receptor NK cells, and monoclonal antibodies targeting inhibitory receptors, which can significantly augment the antitumor activity of NK cells. Notably, emerging evidence suggests that NK cells are a promising constituent of multipronged therapeutic strategies, strengthening immune responses to cancer.
Topics: Cell- and Tissue-Based Therapy; Humans; Immunotherapy; Immunotherapy, Adoptive; Killer Cells, Natural; Neoplasms
PubMed: 34994316
DOI: 10.2174/1574888X17666220107101722 -
Bulletin Du Cancer May 2020
Topics: Bioethical Issues; Bioethics; Blood Preservation; Cell Transplantation; Cord Blood Stem Cell Transplantation; Fetal Blood; France; Humans; Immunotherapy, Adoptive; Lymphocyte Transfusion; Tissue Banks; Tissue Preservation
PubMed: 32386707
DOI: 10.1016/j.bulcan.2020.04.005 -
The Western Journal of Emergency... Apr 2020Cancer therapies have undergone several recent advancements. Current cancer treatments include immune-based therapies comprised of checkpoint inhibitors, and adoptive... (Review)
Review
Cancer therapies have undergone several recent advancements. Current cancer treatments include immune-based therapies comprised of checkpoint inhibitors, and adoptive immunotherapy; each treatment has the potential for complications that differ from chemotherapy and radiation. This review evaluates immune-based therapies and their complications for emergency clinicians. Therapy complications include immune-related adverse events (irAE), cytokine release syndrome (CRS), autoimmune toxicity, and chimeric antigen receptor (CAR) T-cell-related encephalopathy syndrome (CRES). Immune-related adverse events are most commonly encountered with checkpoint inhibitors and include dermatologic complications, pneumonitis, colitis/diarrhea, hepatitis, and endocrinopathies. Less common irAEs include nephritis, myocardial injury, neurologic toxicity, ocular diseases, and musculoskeletal complications. CRS and CRES are more commonly associated with CAR T-cell therapy. CRS commonly presents with flu-like illness and symptoms resembling sepsis, but severe myocardial and pulmonary disease may occur. Critically ill patients require resuscitation, broad-spectrum antibiotics, and hematology/oncology consultation.
Topics: Antineoplastic Agents, Immunological; Emergency Medical Services; Humans; Immune System Diseases; Immunotherapy, Adoptive; Medical Oncology; Neoplasms
PubMed: 32421502
DOI: 10.5811/westjem.2020.1.45898 -
Blood Mar 2024Despite newer targeted therapies, patients with primary refractory or relapsed (r/r) T-cell lymphoma have a poor prognosis. The development of chimeric antigen receptor...
Despite newer targeted therapies, patients with primary refractory or relapsed (r/r) T-cell lymphoma have a poor prognosis. The development of chimeric antigen receptor (CAR) T-cell platforms to treat T-cell malignancies often requires additional gene modifications to overcome fratricide because of shared T-cell antigens on normal and malignant T cells. We developed a CD5-directed CAR that produces minimal fratricide by downmodulating CD5 protein levels in transduced T cells while retaining strong cytotoxicity against CD5+ malignant cells. In our first-in-human phase 1 study (NCT0308190), second-generation autologous CD5.CAR T cells were manufactured from patients with r/r T-cell malignancies. Here, we report safety and efficacy data from a cohort of patients with mature T-cell lymphoma (TCL). Among the 17 patients with TCL enrolled, CD5 CAR T cells were successfully manufactured for 13 out of 14 attempted lines (93%) and administered to 9 (69%) patients. The overall response rate (complete remission or partial response) was 44%, with complete responses observed in 2 patients. The most common grade 3 or higher adverse events were cytopenias. No grade 3 or higher cytokine release syndrome or neurologic events occurred. Two patients died during the immediate toxicity evaluation period due to rapidly progressive disease. These results demonstrated that CD5.CAR T cells are safe and can induce clinical responses in patients with r/r CD5-expressing TCLs without eliminating endogenous T cells or increasing infectious complications. More patients and longer follow-up are needed for validation. This trial was registered at www.clinicaltrials.gov as #NCT0308190.
Topics: Humans; Immunotherapy, Adoptive; Neoplasm Recurrence, Local; T-Lymphocytes; Chronic Disease; Lymphoma, T-Cell; Antigens, CD19
PubMed: 38145560
DOI: 10.1182/blood.2023022204 -
Revista Medica Del Instituto Mexicano... Sep 2019The relationship between cancer and microbes is complex and not entirely known. The objective of this manuscript is to review the scientific evidence on the relationship... (Review)
Review
The relationship between cancer and microbes is complex and not entirely known. The objective of this manuscript is to review the scientific evidence on the relationship between the microbiome, cancer and immunotherapy. A non-systematic literature review was done in the databases MEDLINE, COCHRANE, and DATABASE, and articles of greater scientific rigor, mainly reviews or prospective studies/randomized clinical trials published to date (May 2018), were selected. Terms used in the search included: microbiome, microbiota, cancer, immune checkpoint inhibitors, PD-L1, PD-1 and CTLA-4.
Topics: Gastrointestinal Microbiome; Humans; Immunotherapy, Adoptive; Neoplasms; Probiotics
PubMed: 32568485
DOI: No ID Found -
Medical Oncology (Northwood, London,... Feb 2023Colorectal cancer is prevalent worldwide, with various factors influencing the survival rate of late-stage metastatic cases. Current standard treatments include surgical... (Review)
Review
Colorectal cancer is prevalent worldwide, with various factors influencing the survival rate of late-stage metastatic cases. Current standard treatments include surgical removal, adjuvant chemotherapy, and neoadjuvant chemotherapy. Novel immunotherapy research shows promising results for various cancer types, including colorectal cancer. Current immunotherapy options are limited to specific molecular subtypes of colorectal cancer, while the remaining are limited to standard protocol. This review article summarizes approved, developing, and potential sources for novel colorectal cancer immunotherapy treatment through active-specific, checkpoint inhibitor, cytokine, cytotoxic, and adoptive T-cell immunotherapy. Such a study would be beneficial to patients with colorectal cancer.
Topics: Humans; Immunotherapy; Immunotherapy, Adoptive; Cytokines; Chemotherapy, Adjuvant; Colorectal Neoplasms
PubMed: 36786890
DOI: 10.1007/s12032-023-01967-1